某些β_2-受体激动剂及中药有效成分的毛细管电泳及电化学分析研究
|
摘要
本论文着重研究了三种β2－受体激动剂：克伦特罗、西马特罗和沙丁胺醇的毛细管电泳?安培检测及电化学分析方法，以及中成药藿香正气水中主要有效成分厚朴酚与和厚朴酚的毛细管电泳?安培检测方法。在论文的第一章中，我们对β2－受体激动剂残留分析进展以及中成药有效成分含量测定方法作了概述。提出本论文所要从事的研究工作的设想。
在论文的第二章中，我们采用了循环伏安法(CV)，线性扫描伏安法(LSV)，计时库仑以及恒电位库仑电解法等现代电化学技术详细研究了克伦特罗在玻碳电极上的电化学还原行为。在此基础上建立了灵敏的测定克伦特罗的方波溶出伏安法，并成功地应用于模拟兔血清及尿样中克伦特罗的测定，结果令人满意。
在论文的第三章和第四章中，我们研究了西马特罗和沙丁胺醇在Nafion修饰玻碳电极上的电化学行为，建立了选择性好，灵敏度高的Nafion修饰电极微分脉冲溶出伏安法测定西马特罗以及方波溶出伏安法测定沙丁胺醇的分析方法，使得二者的检测限接近nM级，同时将该体系应用于模拟血清样及尿样中西马特罗和沙丁胺醇的检测，结果令人满意。并结合计时库仑，库仑电解等方法对西马特罗和沙丁胺醇在Nafion修饰玻碳电极上的电化学氧化反应机理进行了探讨，测定了两物质在Nafion膜上的扩散系数、选择性系数和分配系数。
毛细管电泳－电化学检测技术对具有电化学活性的物质的分离检测具有极大的优越性。论文的第五章采用高效毛细管电泳－安培检测法对克伦特罗、西马特罗和沙丁胺醇进行了同时分离检测，上述三种化合物在16min内完全分离。该法重现性好，灵敏度高，线性范围宽，用于模拟饲料及尿样中克伦特罗、西马特罗和沙丁胺醇的分离测定，结果令人满意。
在论文的第六章中，我们在研究厚朴酚及和厚朴酚基本电化学性质的基础上，采用毛细管电泳－安培检测法对霍香正气水中的厚朴酚及和厚朴酚进行了同时分离测定，两待测物在6min以内完全分离，对实际样品的测定获得良好结果。
In this thesis, we have mainly studied on three kinds of β2－agonists, such as clenbuterol, cimaterol and sabutamol, for their simultaneous determination by capillary electrophoresis with amperometric detection(CZE-AD) and their electrochemical properties. We also develop a method for simultaneous determination of honokiol and magnolol in a traditional Chinese medicine, Huo Xiang Zheng Qi Shui, by CZE-AD. In section 1, the progress of the analytical methods for β2－agonists residues and Chinese traditional medicine was reviewed.
In section 2, the electrochemical behavior of clenbuterol was investigated by cyclic voltammetry, linear sweep voltammetry chronocoulometry and bulk electrolysis with coulometry on a glassy carbon electrode. A simple, quick and sensitive method for detection of clenbuterol by Osteryoung Square Wave Stripping Voltammetry was developed. The method was applied to the assay of clenbuterol in rabbit serum and urine with satisfactory results.
In section 3 and section 4, the electrochemical behavior of cimaterol and sabutamol on a Nafion modified electrode was investigated. A high selective and sensitive differential pulse voltammetry method for determination of cimaterol and a simple, quick and sensitive method for detection of sabutamol by Osteryoung Square Wave Stripping Voltammetry were developed, with a low detection limit in the sub nM range. This method was applied to the assay of cimaterol and sabutamol in rabbit serum and urine with good results. The ion-exchange selectivity coefficient, the apparent diffusion coefficient and the distribution coefficient were determined based on the data from experiments of chronocoulometry, bulk electrolysis with coulometry etc.
Since capillary electrophoresis with amperometric detection has great superiority for separation and determination of electrochemical active substances, this method was applied to separation and determination of clenbuterol, cimaterol and sabutamol in section 5. Under the optimum conditions, above three analytes were separated completely within 16 min. The method has been employed for the determination of clenbuterol, cimaterol and sabutamol in rabbit urine and feed by standard addition with satisfactory results.
In section 6, based on the investigation of the electrochemical characteristics of honokiol and magnolol, a method for simultaneous separation and detection of honokiol and magnolol in the traditional Chinese medicine, Huo Xiang Zheng Qi Shui, by capillary electrophoresis with amperometric detection was developed. Under the optimum conditions, the analytes were separated completely within 6 min, and the good results for the real samples were obtained.
在论文的第二章中，我们采用了循环伏安法(CV)，线性扫描伏安法(LSV)，计时库仑以及恒电位库仑电解法等现代电化学技术详细研究了克伦特罗在玻碳电极上的电化学还原行为。在此基础上建立了灵敏的测定克伦特罗的方波溶出伏安法，并成功地应用于模拟兔血清及尿样中克伦特罗的测定，结果令人满意。
在论文的第三章和第四章中，我们研究了西马特罗和沙丁胺醇在Nafion修饰玻碳电极上的电化学行为，建立了选择性好，灵敏度高的Nafion修饰电极微分脉冲溶出伏安法测定西马特罗以及方波溶出伏安法测定沙丁胺醇的分析方法，使得二者的检测限接近nM级，同时将该体系应用于模拟血清样及尿样中西马特罗和沙丁胺醇的检测，结果令人满意。并结合计时库仑，库仑电解等方法对西马特罗和沙丁胺醇在Nafion修饰玻碳电极上的电化学氧化反应机理进行了探讨，测定了两物质在Nafion膜上的扩散系数、选择性系数和分配系数。
毛细管电泳－电化学检测技术对具有电化学活性的物质的分离检测具有极大的优越性。论文的第五章采用高效毛细管电泳－安培检测法对克伦特罗、西马特罗和沙丁胺醇进行了同时分离检测，上述三种化合物在16min内完全分离。该法重现性好，灵敏度高，线性范围宽，用于模拟饲料及尿样中克伦特罗、西马特罗和沙丁胺醇的分离测定，结果令人满意。
在论文的第六章中，我们在研究厚朴酚及和厚朴酚基本电化学性质的基础上，采用毛细管电泳－安培检测法对霍香正气水中的厚朴酚及和厚朴酚进行了同时分离测定，两待测物在6min以内完全分离，对实际样品的测定获得良好结果。
In this thesis, we have mainly studied on three kinds of β2－agonists, such as clenbuterol, cimaterol and sabutamol, for their simultaneous determination by capillary electrophoresis with amperometric detection(CZE-AD) and their electrochemical properties. We also develop a method for simultaneous determination of honokiol and magnolol in a traditional Chinese medicine, Huo Xiang Zheng Qi Shui, by CZE-AD. In section 1, the progress of the analytical methods for β2－agonists residues and Chinese traditional medicine was reviewed.
In section 2, the electrochemical behavior of clenbuterol was investigated by cyclic voltammetry, linear sweep voltammetry chronocoulometry and bulk electrolysis with coulometry on a glassy carbon electrode. A simple, quick and sensitive method for detection of clenbuterol by Osteryoung Square Wave Stripping Voltammetry was developed. The method was applied to the assay of clenbuterol in rabbit serum and urine with satisfactory results.
In section 3 and section 4, the electrochemical behavior of cimaterol and sabutamol on a Nafion modified electrode was investigated. A high selective and sensitive differential pulse voltammetry method for determination of cimaterol and a simple, quick and sensitive method for detection of sabutamol by Osteryoung Square Wave Stripping Voltammetry were developed, with a low detection limit in the sub nM range. This method was applied to the assay of cimaterol and sabutamol in rabbit serum and urine with good results. The ion-exchange selectivity coefficient, the apparent diffusion coefficient and the distribution coefficient were determined based on the data from experiments of chronocoulometry, bulk electrolysis with coulometry etc.
Since capillary electrophoresis with amperometric detection has great superiority for separation and determination of electrochemical active substances, this method was applied to separation and determination of clenbuterol, cimaterol and sabutamol in section 5. Under the optimum conditions, above three analytes were separated completely within 16 min. The method has been employed for the determination of clenbuterol, cimaterol and sabutamol in rabbit urine and feed by standard addition with satisfactory results.
In section 6, based on the investigation of the electrochemical characteristics of honokiol and magnolol, a method for simultaneous separation and detection of honokiol and magnolol in the traditional Chinese medicine, Huo Xiang Zheng Qi Shui, by capillary electrophoresis with amperometric detection was developed. Under the optimum conditions, the analytes were separated completely within 6 min, and the good results for the real samples were obtained.
引文
[1] 孙庆安，顾新生，濮紫兰，兽药残留分析，上海科学技术出版社，2002，2，641
[2] Baker P K, Lierman J A. Derivatives for enhancing the growth rate of meat
producing animals and improving the efficiency of feed utilization, US Patent No.4 404 222,1983
[3] Allen P, Quirke J F, Tarrent P V. Effects of CIM on the growth, food efficiency and carcass quality of Friesian cattle. In: Hanrahan J P Ed. Beta-agonist and their Effects on Animal Growth and Carcass Quality, 1987,83
[4] Haasnort W ,Stouten P, Lommen A, et al.Analyst,1994, 119: 2675
[5] Reed P J, Hay S M, Dorwood P M,et al. Br J Nutr, 1986,56:249
[6] Wulliams P E V, Pagliani L, Innes G M, et al. Br J Nutr. 1987,57:417
[7] Adeola O ,Darko E A ,He P ,et al.J Anim Sci,1990,68:3633
[8] Joes R W, Easter R A,McKeith F K,et al.J Anim Sci,1985,61:905
[9] Beerman D H, Butler W R, Hogue D E,et al. J Anim Sci, 1987,65:1514
[10] 杨珊瑛.反相离子对HPLC法测定情安喘定片中微量盐酸克伦特罗[J].中草药，1999，30（9）：368-370
[11] 姜金霞，钟建平，张胜全.HPLC法测定皮肤渗透液中克喘素含量[J].药物分析杂志，1992，12（2）：118-119
[12] P.Gonzalez Gigosos, C.A.Febte Smpayo and C. Franco Abuin, et al.[J]. Chromatographia, 1996, 43(5/6):271-274
[13] D.J.Smith, Helga Sauerwein , et al.[J].Clinical Chemisty,1996,42(11):
1869-1870
[14] Leyssens L,van de Greef J,Penxten H, et al. Structure elucidation of unknown clenbuterol analogues detected in illegal preparation for animal use, Procedings of the Euroresidue Ⅱ Conference, Veldhoven, The Netherland,1993,444
[15] 周光宏，韩正康。中国畜牧杂志，1993，29（1）：14
[16] G. H. Zhou & Z.K. HAN 1994.British Poultry Science,35:355
[17] MacRae, J, C.et al. The effect of the β-adrenergic agonist clenbuterol on the energy expenditure& protein turnover of wetheer lambs.J.Anim.Sci, 1986, 63 (Suppl.1):453
[18] Eisemann J. H. et al.J.Anim. Sci,1988,66:342-353
[19] Kanakar Pou, Huy Ong and Albert Adam Kunakar. [J]. Analyst, 1994,119(12):2659-2662
[20] Delahaut P, Dubois M, et al. [J].Food. Additives and Contaminants, 1991,8(1):43-53
[21] Smith D J, Feil V J, Huwe J K, et al.Drug Metab Dispos,1993,21:624
[22] Smith D J, Giddings J M, Feil V J,et al.Xenobiotica,1995,25:511
[23] Horiba M, Muria T, Nomura K, et al. Arzneim-Forsch/Drug Res,1984,34:1668
[24] Loo J C K, Beaulieu N, Jordan N,et al.Commun Chem Pathol Pharmacol,1987,55:283
[25] L. Leyssens, C Driessen, A Driessen,A Jacobs. Journal of Chromatography, 1991,564:515-219
[26] Polettini J,Ricossa M C, Groppi A, et al.J Chromatogr, 1991,564:529
[27] Boyd D, Rodriguezz B J R, Blanco T P, et al. J Biomed Pharm Anal,1994,12:1069
[28] Hutchings M J, Paull J D, Morgan D J. J Chromatogr, 1883,277:423
[29] Wu Y Q, Shi R, Williams R L, et al. J Liq Chromatogr,1991,14:253
[30] Tan Y K, Soldin S J. J Chromatogr,1984,36:311
[31] Miller L G, Greenblatt D J. J Chromatogr, 1986,381:205
[32] Courtheyn D, Desaever C, Verhe R. J Chromatog, 1991,564:537
[33] Degroodt J M,deBukanski W B, Beemaet H, et al. Z Lebnsm Unter Forsch, 1989,189:128
[34] Eddins C,Hamann J,Johnson K. J Chromatogr Sci,1985,23:308
[35] Migazaki T. J Food Hygienic Soc Japan, 1995,36(2):269
[36] Montrade M P. Anal Chim Acta,1993,275(1-2):253
[37] Meyer H H D, Rinke L, Dursch I. J Chromatogr, 1991,564:551-556
[38] de Groof J, Degroodt J M, de Bukanski B W, et al. Z Lebensm Forsch, 1991,193:126
[39] Haunch M, Grugger E. Dtsch Lebensm-Rundsch,1989,85:178
[40] Emm T, Lesco L J, lislie J, et al.J Chromatogr, 1988,427:188
[41] Leis H J, Gleispach H, Nitsche V, et al. Biomed Environ Mass Spectrom,1990:382
[42] Leferink J G, Dankers J,Maes R A A. J Chromatogr, 1982,229:217
[43] Lindberg C, Jonsson S, Paulson J, et al. Biomed Environ Mass Spectrom,1990,19:218
[44] Turberg M P,Macy T D,Lewis J J, et al. J AOAC Int, 1995,78(6):1394
[45] Bland R E, Tanner R J N,Chen W H,et al. J Pharm Biomed Anal,1990,8:591
[46] McCarthy P T, Atwal S,Sykes A P, et al. Biomed Chromatogr,1993,7:25
[47] Bower G D, Higton D M, Manchee G R,et al. J Chromatogr, 1991,554:175
[48] Colthup P V, Dallas F A A,Saynor D A, et al. J Chromatogr, 1985:345:111
[49] Jacobsson S E, Jonsson S, Lindberg C, et al. Biomed Mass Spectrom, 1980,7:265
[50] Vanoosthuyze K E I, Arts C J M, Van Peteghem C H. J Agric Food Chem,
1997,45(8):3129
[51] Ladka H. Eluntersuchung and Hygiene, 1995,86(5):526
[52] Hashimoto T. J Food Hygienic Soc Japan,1995,36(6):754
[53] Dumasia M C, Houghton E. J Chromatogr, 1991,564:503
[54] Gabilia C. Proceedings of the EuroResidue 2 Conference Veldhoven. The Netherland, May 3-5,1993. Haagsma N, Ruiter A Eds, 289
[55] Collins S, O'Keeffe M, Smyth M R. Analyst, 1994,119:2671
[56] Long A R, Hsieh L C,Malbrough M S,et al. J AOAC Int, 1990,73:379
[57] Long A R, Hsieh L C,Malbrough M S,et al. J Agric Food Chem, 1990,38:423
[58] Boyd D, Shearan P, Hopkins J P,et al. Anal Chim Acta,1993,275:221
[59] Boyd D, Shearan P, Hopkins J P,et al. Anal Proc, 1993,30:156
[60] Boyd D, O'Keeffe M, Smyth R. Analyst,1994,119:1467
[61] Haagsnoot W, Ploum M E, Paulussen R J A, et al. J Chromatogr, 1990,519:323
[62] Rashid B, Kwasowski P, Stevenson D. Methodol Surv Bioanal Drugs,1996,24:219
[63] Pickett R J H, Sauer M J. Anal. Chim. Acta, 1993,275:269-273
[64] Ramos F, Castilho M C, da Silveira I N, et al. Anal Chim. Acta, 1993,275:279
[65] Cooper A D, Shepherd M J. Food Agric Immunol,1996,8(3):205
[66] Van Ginkel L A, Stephany R W, van Rossum H J. J AOAC Int.,1992,75(3):554
[67] Lawrence J F, Menard C. J Chromatogr, B: Biomed Sci Appl,1997,696(2):291
[68] Nausch T. Archiv Fur Lebensmittelhygiene,1997,48(3):56
[69] Brambilla G, Fiori M, Rizzo B, et al. J Chromatogr B,2001,759:27
[70] Schmeer K, Sauter T, Schmid J. J Chromatogr, A, 1997,777(1):67
[71] Sagar K, Kelly M T, Smyth M R. J Chromatogr,1992,115:109
[72] Edholm L E, Kennedy B M, Berquist S. Chromatographia,1992,16:341
[73] Berquist S, Edholm L E, J liq Chromatogr,1983,6:559
[74] Tamisier-Karolak T, Delhotal-Landes B, Jolliet-Riant P,et al. The Drug Monit,1992,14:327
[75] Visser T, Vredenbregt M J, de Jong A P J M, et al. Analyst, 1994, 119:2681
[76] de Groodt J M, de Bukanski W, de Groof J, et al. Z Lenbensm Unters Forsch, 1991,192:430
[77] Biondi P A, Guidotti L, Montana M, et al J Chromatogr Sci, 1991,29:190
[78] Lau B P-Y Lewis, D Lawrence J F. J Mass Spectrom, 1997,32(6):655
[79] Buyse J, Deycupere E, Iluyghebaert M J. Poultry Science,1991,70:992-1002
[80] 刘欣，张亦中，张长久等。人尿中沙丁胺醇的测定[J],药学学报，1994，29（6）：454～458
[81] 冯杰等。饲料中克伦特罗的气相色谱－质谱联用法测定，动物营养学报，2000，12（4）：48－50
[82] Harkins J D. Woods W E ,Lehner A F, et al. J Ver Pharmacol Ther ,2001, 24(1):7-14
[83] Abukhalaf I K, Von Deutsch D A, et al.Biomed Chromatogr.,2000,14(2):99-105
[84] T. Visser , M.J. Vredenbregt and A. P. J.M. De Jong. [J]. Analytical Chimica Acta, 1993,27(5): 205-214
[85] Roger T, Wilson Joseph , M. Grinecek Kathleen, P. Holland, et al. Journal of AOAc international, 1994,77(4):917-924
[86] Peter Batjoens, Dirk Courtheyn, Huber F, et al. Journal of Chromatography A,
1996,750:133-139
[87] D.J.Smith. Sterochemical composition of Clenbuterol Residues in edible tissue of swine [J]. J. Agric. Food Chem. 2000,48:6036-6043
[88] Fente C A, Vazques B I, Franco C, et al. Journal of Chromatography B, 1999,726:133-139
[89] 中华人民共和国卫生部GB16869－2000，附录B
[90] 赵榕，等.反相HPLC发测定猪肝中盐酸克伦特罗[J].中国食品卫生杂志，2000，12（2）：22－24
[91] 蔡玉枝，等.HPLC法测定猪组织中盐酸克伦特罗残留量[J].中国卫生检验杂志，2002，4:193－194
[92] 方炳虎，等.克伦特罗在猪体内的生物利用度及药物动力学研究[J].畜牧兽医学报，1997，28（3）：233－237
[93] 秦永平，等.反相高效液相色谱－紫外检测法测定血浆中沙丁胺醇浓度[J]中国药学杂志，2000，7：475－477
[94] Tsai CE,Kondo F. Liquid chromatographic determination of salbutamol and clenbuterol residues in swine serum and muscle J. Microbios 1994;80(325):251-258
[95] 付民，等.固相萃取高效液相色谱法测定血浆中沙丁胺醇[J].中国医药工业杂志，2001，32（3）：123－125
[96] Lin L A, Tomlinson J A, Satzger R D. J Chromatogr A,1997,762(1/2):275
[97] Gleixner A, Sauerwein H, Meyer H H D.Food Addit Contam, 1997,14(2):143
[98] Kaita De Wach, Hubert De Brabander and Dirk Courthevn. LC-MS-MS to detect and identify four beta-agonist and quantify clenbuterol in tissue liver J. Analyst,1998,123:2701-2705
[99] Doerge D R, Churchwell M I, Holder C L, et al. Anal Chem, 1996,68(11):1918
[100] Laurrent Debrauwer and Geoges Bories.[J]. Analytica Chimica Acta, 1993,27(5):231-239
[101] 陈继明，龚晓明，陆承平，等。[J].南京农业大学学报，1998，21：81-88
[102] 陈继明，黄士新，陆承平，等。[J].中国兽药杂志，1999，33（2）：19-22
[103] 孔科，袁宗辉，范盛先，[J].华中农业大学学报，2000，19（3）：252-255
[104] Guy Degand and Anne Bernes Duckaerts. [J].Analytica Chimica Acta, 1993,
27(5):241-247
[105] Adam A, Gercais N, Panoyan A and Ong H. [J]. Analyst ,1994,119(12):2663-2666
[106] Weilin L Shelver and David J Smith. [J]. Food Additives and Contaminants, 2000,17(10):837-845
[107] Kristia Na, Ew I Vancosthuyze, Cor J. M. Arrts and Carlos H. Van Peteghen. [J]. Agric food Chem, 1997, 45(8):3129-3137
[108] S.D. Bucknall, A. L.Mackenzi, M.J.Sauer ,et al. [J].Analytical Chimica Acta, 1993,27(5):227-230
[109] C T Elliott, S R H Crooks, W J Mc Caughey, et al. Veterinary Record, 1995,137:643-644
[110] Hagedore, H. W. Zuck, S., and Sohulz, R. J of Veterinary Medicine. Series A, 1995,42(3):209-219
[111] Smith DJ. [J].J Animal Science, 2000 ,78(11):2903-2912
[112] Bacigalupo MA, Ius A, et al. J. Analyst, 1995 Aug;120(8):2269-2271
[113] Elliott C T, Baxter A, Haasnoot W, et al. Food Agric Immunol,1996,8:219
[114] Smyth W F, Harland G B, McClean S, et al. J Chromatogr, A, 1997, 772(1/2):161
[115] Altria K D, Kelly M A, Clark B J. Chromatographia, 1996, 43(3/4):153
[116] Sangiorgi E, Curatlo M. J Chromatogr, B: Biomed Sci Appl, 1997, 693(2):468
[117] Plsyniak A. Polish J. Environ Studies, 1995, 5(5):33
[118] Biosca Y M, Baeza J J, Ramis-Ramos G. J Pharm Biomed Anal, 1996, 14(8-10):1037
[119] Moane S, Smyth M R, O'Keeffe M. Analyst , 1996, 121(6):779
[120] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第二十册，1998，324
[121] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第八册，1993，87
[122] 卫生部药典委员会. 中国药典[M].一部.北京：化学工业出版社，2000，321-637
[123] 徐燕，邵家德.[J]. 中国药事，1997，11（4）：250
[124] 戴明宽，陈为飞.[J]. 中国药事，1999，13（2）：117
[125] 宋祥满，官玉民. [J]. 中国药事，1998，12（4）：225
[126] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第十四册，1997，122
[127] 姚桂根. [J].中成药研究，1987，（9）：36
[128] 卫生部药典委员会. 中国药典[M].一部.北京：化学工业出版社，2000，332
[129] 徐勤，刘布鸣，张正行. [J].中国药学杂志，2001，36（2）：122
[130] 张丽明，白鸥. [J].中国药学杂志，1997，32（9）：568
[131] 徐国兵，汪国孙. [J].中国药学杂志，2000，35（6）：411
[132] 高素强，傅得兴，宋友华等. [J].中国药学杂志，1999，34（12）：843
[133] 万绍晖，束刚，张萱等. [J].中国药学杂志，1997，32（2）：108
[134] 刘伟，梁生旺. [J].中国药学杂志，1999，34（10）：689
[135] 倪晟，赵培洁，郑燕等. [J].中国药学杂志，1999，34（1）：45
[136] 冯广武，赵仁庚，张军平等. [J].中国药学杂志，1999，34（9）：621
[137] 梁生旺，朱新成，焦振等. [J].中国药学杂志，1997，32（6）：368
[138] S.J.Seu,etal. Anal. Chim. Acta, 309(1995)361
[139] 张国华等. 色谱，13(1995)247
[140] H. Y. Huang, etal. J.Chromatogr. A, 771(1997)267
[141] Y.Z.Hsieh, etal. J.Chromatogr. A, 75(1997)193
[142] Fumihiko Yoshizaki, etal. ShoyakugakuZasshi, 51(1997)550
[143] C.Y.Wang, etal. J.Chromatogr. A,802(1998)225
[144] Y.R.Ku, etal. J. Chromatogr. A, 805(1998)301
[145] J.J.Yang, etal. J.Chromatogr. A, 811(1998)274
[146] Y.R. Ku, etal. Chin. Pharm. J., 50(1998)157
[147] 林梅等.分析化学，26(1998)457
[148] 林梅等.中草药，29(1998)518
[149] Z. L.Fang, etal. Anal. Chim. Acta, 346(1997)135
[150] 沈琦等.分析实验室，17(1998)1。
[2] Baker P K, Lierman J A. Derivatives for enhancing the growth rate of meat
producing animals and improving the efficiency of feed utilization, US Patent No.4 404 222,1983
[3] Allen P, Quirke J F, Tarrent P V. Effects of CIM on the growth, food efficiency and carcass quality of Friesian cattle. In: Hanrahan J P Ed. Beta-agonist and their Effects on Animal Growth and Carcass Quality, 1987,83
[4] Haasnort W ,Stouten P, Lommen A, et al.Analyst,1994, 119: 2675
[5] Reed P J, Hay S M, Dorwood P M,et al. Br J Nutr, 1986,56:249
[6] Wulliams P E V, Pagliani L, Innes G M, et al. Br J Nutr. 1987,57:417
[7] Adeola O ,Darko E A ,He P ,et al.J Anim Sci,1990,68:3633
[8] Joes R W, Easter R A,McKeith F K,et al.J Anim Sci,1985,61:905
[9] Beerman D H, Butler W R, Hogue D E,et al. J Anim Sci, 1987,65:1514
[10] 杨珊瑛.反相离子对HPLC法测定情安喘定片中微量盐酸克伦特罗[J].中草药，1999，30（9）：368-370
[11] 姜金霞，钟建平，张胜全.HPLC法测定皮肤渗透液中克喘素含量[J].药物分析杂志，1992，12（2）：118-119
[12] P.Gonzalez Gigosos, C.A.Febte Smpayo and C. Franco Abuin, et al.[J]. Chromatographia, 1996, 43(5/6):271-274
[13] D.J.Smith, Helga Sauerwein , et al.[J].Clinical Chemisty,1996,42(11):
1869-1870
[14] Leyssens L,van de Greef J,Penxten H, et al. Structure elucidation of unknown clenbuterol analogues detected in illegal preparation for animal use, Procedings of the Euroresidue Ⅱ Conference, Veldhoven, The Netherland,1993,444
[15] 周光宏，韩正康。中国畜牧杂志，1993，29（1）：14
[16] G. H. Zhou & Z.K. HAN 1994.British Poultry Science,35:355
[17] MacRae, J, C.et al. The effect of the β-adrenergic agonist clenbuterol on the energy expenditure& protein turnover of wetheer lambs.J.Anim.Sci, 1986, 63 (Suppl.1):453
[18] Eisemann J. H. et al.J.Anim. Sci,1988,66:342-353
[19] Kanakar Pou, Huy Ong and Albert Adam Kunakar. [J]. Analyst, 1994,119(12):2659-2662
[20] Delahaut P, Dubois M, et al. [J].Food. Additives and Contaminants, 1991,8(1):43-53
[21] Smith D J, Feil V J, Huwe J K, et al.Drug Metab Dispos,1993,21:624
[22] Smith D J, Giddings J M, Feil V J,et al.Xenobiotica,1995,25:511
[23] Horiba M, Muria T, Nomura K, et al. Arzneim-Forsch/Drug Res,1984,34:1668
[24] Loo J C K, Beaulieu N, Jordan N,et al.Commun Chem Pathol Pharmacol,1987,55:283
[25] L. Leyssens, C Driessen, A Driessen,A Jacobs. Journal of Chromatography, 1991,564:515-219
[26] Polettini J,Ricossa M C, Groppi A, et al.J Chromatogr, 1991,564:529
[27] Boyd D, Rodriguezz B J R, Blanco T P, et al. J Biomed Pharm Anal,1994,12:1069
[28] Hutchings M J, Paull J D, Morgan D J. J Chromatogr, 1883,277:423
[29] Wu Y Q, Shi R, Williams R L, et al. J Liq Chromatogr,1991,14:253
[30] Tan Y K, Soldin S J. J Chromatogr,1984,36:311
[31] Miller L G, Greenblatt D J. J Chromatogr, 1986,381:205
[32] Courtheyn D, Desaever C, Verhe R. J Chromatog, 1991,564:537
[33] Degroodt J M,deBukanski W B, Beemaet H, et al. Z Lebnsm Unter Forsch, 1989,189:128
[34] Eddins C,Hamann J,Johnson K. J Chromatogr Sci,1985,23:308
[35] Migazaki T. J Food Hygienic Soc Japan, 1995,36(2):269
[36] Montrade M P. Anal Chim Acta,1993,275(1-2):253
[37] Meyer H H D, Rinke L, Dursch I. J Chromatogr, 1991,564:551-556
[38] de Groof J, Degroodt J M, de Bukanski B W, et al. Z Lebensm Forsch, 1991,193:126
[39] Haunch M, Grugger E. Dtsch Lebensm-Rundsch,1989,85:178
[40] Emm T, Lesco L J, lislie J, et al.J Chromatogr, 1988,427:188
[41] Leis H J, Gleispach H, Nitsche V, et al. Biomed Environ Mass Spectrom,1990:382
[42] Leferink J G, Dankers J,Maes R A A. J Chromatogr, 1982,229:217
[43] Lindberg C, Jonsson S, Paulson J, et al. Biomed Environ Mass Spectrom,1990,19:218
[44] Turberg M P,Macy T D,Lewis J J, et al. J AOAC Int, 1995,78(6):1394
[45] Bland R E, Tanner R J N,Chen W H,et al. J Pharm Biomed Anal,1990,8:591
[46] McCarthy P T, Atwal S,Sykes A P, et al. Biomed Chromatogr,1993,7:25
[47] Bower G D, Higton D M, Manchee G R,et al. J Chromatogr, 1991,554:175
[48] Colthup P V, Dallas F A A,Saynor D A, et al. J Chromatogr, 1985:345:111
[49] Jacobsson S E, Jonsson S, Lindberg C, et al. Biomed Mass Spectrom, 1980,7:265
[50] Vanoosthuyze K E I, Arts C J M, Van Peteghem C H. J Agric Food Chem,
1997,45(8):3129
[51] Ladka H. Eluntersuchung and Hygiene, 1995,86(5):526
[52] Hashimoto T. J Food Hygienic Soc Japan,1995,36(6):754
[53] Dumasia M C, Houghton E. J Chromatogr, 1991,564:503
[54] Gabilia C. Proceedings of the EuroResidue 2 Conference Veldhoven. The Netherland, May 3-5,1993. Haagsma N, Ruiter A Eds, 289
[55] Collins S, O'Keeffe M, Smyth M R. Analyst, 1994,119:2671
[56] Long A R, Hsieh L C,Malbrough M S,et al. J AOAC Int, 1990,73:379
[57] Long A R, Hsieh L C,Malbrough M S,et al. J Agric Food Chem, 1990,38:423
[58] Boyd D, Shearan P, Hopkins J P,et al. Anal Chim Acta,1993,275:221
[59] Boyd D, Shearan P, Hopkins J P,et al. Anal Proc, 1993,30:156
[60] Boyd D, O'Keeffe M, Smyth R. Analyst,1994,119:1467
[61] Haagsnoot W, Ploum M E, Paulussen R J A, et al. J Chromatogr, 1990,519:323
[62] Rashid B, Kwasowski P, Stevenson D. Methodol Surv Bioanal Drugs,1996,24:219
[63] Pickett R J H, Sauer M J. Anal. Chim. Acta, 1993,275:269-273
[64] Ramos F, Castilho M C, da Silveira I N, et al. Anal Chim. Acta, 1993,275:279
[65] Cooper A D, Shepherd M J. Food Agric Immunol,1996,8(3):205
[66] Van Ginkel L A, Stephany R W, van Rossum H J. J AOAC Int.,1992,75(3):554
[67] Lawrence J F, Menard C. J Chromatogr, B: Biomed Sci Appl,1997,696(2):291
[68] Nausch T. Archiv Fur Lebensmittelhygiene,1997,48(3):56
[69] Brambilla G, Fiori M, Rizzo B, et al. J Chromatogr B,2001,759:27
[70] Schmeer K, Sauter T, Schmid J. J Chromatogr, A, 1997,777(1):67
[71] Sagar K, Kelly M T, Smyth M R. J Chromatogr,1992,115:109
[72] Edholm L E, Kennedy B M, Berquist S. Chromatographia,1992,16:341
[73] Berquist S, Edholm L E, J liq Chromatogr,1983,6:559
[74] Tamisier-Karolak T, Delhotal-Landes B, Jolliet-Riant P,et al. The Drug Monit,1992,14:327
[75] Visser T, Vredenbregt M J, de Jong A P J M, et al. Analyst, 1994, 119:2681
[76] de Groodt J M, de Bukanski W, de Groof J, et al. Z Lenbensm Unters Forsch, 1991,192:430
[77] Biondi P A, Guidotti L, Montana M, et al J Chromatogr Sci, 1991,29:190
[78] Lau B P-Y Lewis, D Lawrence J F. J Mass Spectrom, 1997,32(6):655
[79] Buyse J, Deycupere E, Iluyghebaert M J. Poultry Science,1991,70:992-1002
[80] 刘欣，张亦中，张长久等。人尿中沙丁胺醇的测定[J],药学学报，1994，29（6）：454～458
[81] 冯杰等。饲料中克伦特罗的气相色谱－质谱联用法测定，动物营养学报，2000，12（4）：48－50
[82] Harkins J D. Woods W E ,Lehner A F, et al. J Ver Pharmacol Ther ,2001, 24(1):7-14
[83] Abukhalaf I K, Von Deutsch D A, et al.Biomed Chromatogr.,2000,14(2):99-105
[84] T. Visser , M.J. Vredenbregt and A. P. J.M. De Jong. [J]. Analytical Chimica Acta, 1993,27(5): 205-214
[85] Roger T, Wilson Joseph , M. Grinecek Kathleen, P. Holland, et al. Journal of AOAc international, 1994,77(4):917-924
[86] Peter Batjoens, Dirk Courtheyn, Huber F, et al. Journal of Chromatography A,
1996,750:133-139
[87] D.J.Smith. Sterochemical composition of Clenbuterol Residues in edible tissue of swine [J]. J. Agric. Food Chem. 2000,48:6036-6043
[88] Fente C A, Vazques B I, Franco C, et al. Journal of Chromatography B, 1999,726:133-139
[89] 中华人民共和国卫生部GB16869－2000，附录B
[90] 赵榕，等.反相HPLC发测定猪肝中盐酸克伦特罗[J].中国食品卫生杂志，2000，12（2）：22－24
[91] 蔡玉枝，等.HPLC法测定猪组织中盐酸克伦特罗残留量[J].中国卫生检验杂志，2002，4:193－194
[92] 方炳虎，等.克伦特罗在猪体内的生物利用度及药物动力学研究[J].畜牧兽医学报，1997，28（3）：233－237
[93] 秦永平，等.反相高效液相色谱－紫外检测法测定血浆中沙丁胺醇浓度[J]中国药学杂志，2000，7：475－477
[94] Tsai CE,Kondo F. Liquid chromatographic determination of salbutamol and clenbuterol residues in swine serum and muscle J. Microbios 1994;80(325):251-258
[95] 付民，等.固相萃取高效液相色谱法测定血浆中沙丁胺醇[J].中国医药工业杂志，2001，32（3）：123－125
[96] Lin L A, Tomlinson J A, Satzger R D. J Chromatogr A,1997,762(1/2):275
[97] Gleixner A, Sauerwein H, Meyer H H D.Food Addit Contam, 1997,14(2):143
[98] Kaita De Wach, Hubert De Brabander and Dirk Courthevn. LC-MS-MS to detect and identify four beta-agonist and quantify clenbuterol in tissue liver J. Analyst,1998,123:2701-2705
[99] Doerge D R, Churchwell M I, Holder C L, et al. Anal Chem, 1996,68(11):1918
[100] Laurrent Debrauwer and Geoges Bories.[J]. Analytica Chimica Acta, 1993,27(5):231-239
[101] 陈继明，龚晓明，陆承平，等。[J].南京农业大学学报，1998，21：81-88
[102] 陈继明，黄士新，陆承平，等。[J].中国兽药杂志，1999，33（2）：19-22
[103] 孔科，袁宗辉，范盛先，[J].华中农业大学学报，2000，19（3）：252-255
[104] Guy Degand and Anne Bernes Duckaerts. [J].Analytica Chimica Acta, 1993,
27(5):241-247
[105] Adam A, Gercais N, Panoyan A and Ong H. [J]. Analyst ,1994,119(12):2663-2666
[106] Weilin L Shelver and David J Smith. [J]. Food Additives and Contaminants, 2000,17(10):837-845
[107] Kristia Na, Ew I Vancosthuyze, Cor J. M. Arrts and Carlos H. Van Peteghen. [J]. Agric food Chem, 1997, 45(8):3129-3137
[108] S.D. Bucknall, A. L.Mackenzi, M.J.Sauer ,et al. [J].Analytical Chimica Acta, 1993,27(5):227-230
[109] C T Elliott, S R H Crooks, W J Mc Caughey, et al. Veterinary Record, 1995,137:643-644
[110] Hagedore, H. W. Zuck, S., and Sohulz, R. J of Veterinary Medicine. Series A, 1995,42(3):209-219
[111] Smith DJ. [J].J Animal Science, 2000 ,78(11):2903-2912
[112] Bacigalupo MA, Ius A, et al. J. Analyst, 1995 Aug;120(8):2269-2271
[113] Elliott C T, Baxter A, Haasnoot W, et al. Food Agric Immunol,1996,8:219
[114] Smyth W F, Harland G B, McClean S, et al. J Chromatogr, A, 1997, 772(1/2):161
[115] Altria K D, Kelly M A, Clark B J. Chromatographia, 1996, 43(3/4):153
[116] Sangiorgi E, Curatlo M. J Chromatogr, B: Biomed Sci Appl, 1997, 693(2):468
[117] Plsyniak A. Polish J. Environ Studies, 1995, 5(5):33
[118] Biosca Y M, Baeza J J, Ramis-Ramos G. J Pharm Biomed Anal, 1996, 14(8-10):1037
[119] Moane S, Smyth M R, O'Keeffe M. Analyst , 1996, 121(6):779
[120] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第二十册，1998，324
[121] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第八册，1993，87
[122] 卫生部药典委员会. 中国药典[M].一部.北京：化学工业出版社，2000，321-637
[123] 徐燕，邵家德.[J]. 中国药事，1997，11（4）：250
[124] 戴明宽，陈为飞.[J]. 中国药事，1999，13（2）：117
[125] 宋祥满，官玉民. [J]. 中国药事，1998，12（4）：225
[126] 卫生部药典委员会. 中华人民共和国卫生部药品标准 [s]. 中药成方剂.第十四册，1997，122
[127] 姚桂根. [J].中成药研究，1987，（9）：36
[128] 卫生部药典委员会. 中国药典[M].一部.北京：化学工业出版社，2000，332
[129] 徐勤，刘布鸣，张正行. [J].中国药学杂志，2001，36（2）：122
[130] 张丽明，白鸥. [J].中国药学杂志，1997，32（9）：568
[131] 徐国兵，汪国孙. [J].中国药学杂志，2000，35（6）：411
[132] 高素强，傅得兴，宋友华等. [J].中国药学杂志，1999，34（12）：843
[133] 万绍晖，束刚，张萱等. [J].中国药学杂志，1997，32（2）：108
[134] 刘伟，梁生旺. [J].中国药学杂志，1999，34（10）：689
[135] 倪晟，赵培洁，郑燕等. [J].中国药学杂志，1999，34（1）：45
[136] 冯广武，赵仁庚，张军平等. [J].中国药学杂志，1999，34（9）：621
[137] 梁生旺，朱新成，焦振等. [J].中国药学杂志，1997，32（6）：368
[138] S.J.Seu,etal. Anal. Chim. Acta, 309(1995)361
[139] 张国华等. 色谱，13(1995)247
[140] H. Y. Huang, etal. J.Chromatogr. A, 771(1997)267
[141] Y.Z.Hsieh, etal. J.Chromatogr. A, 75(1997)193
[142] Fumihiko Yoshizaki, etal. ShoyakugakuZasshi, 51(1997)550
[143] C.Y.Wang, etal. J.Chromatogr. A,802(1998)225
[144] Y.R.Ku, etal. J. Chromatogr. A, 805(1998)301
[145] J.J.Yang, etal. J.Chromatogr. A, 811(1998)274
[146] Y.R. Ku, etal. Chin. Pharm. J., 50(1998)157
[147] 林梅等.分析化学，26(1998)457
[148] 林梅等.中草药，29(1998)518
[149] Z. L.Fang, etal. Anal. Chim. Acta, 346(1997)135
[150] 沈琦等.分析实验室，17(1998)1。